Age-depending effects of methotrexate treatment on systemic bone turnover in experimental adjuvant arthritis

Adjuvant arthritis was induced in rats in the growth stage (aged 6 weeks) a nd those in the mature stage (aed 4 months), and changes in the systemic bo ne turnover and the effects of methotrexate (MTX, CAS 133073-73-1) were com pared. After induction of adjuvant arthritis, the paw edema ratio and the urinary deoxypylidinoline (u-Dpy) level increased in both age groups. No marked cha nges were observed in the serum osteocalcin (s-OC) level in either group. I n the 6-week-old rats. arthritis completely inhibited the bone mass, and st rength of the femur and lumbar vertebral body. The 4-month-old rats showed more marked changes than the 6-week-old rats in the bone mass and strength of the lumbar, vertebral body. MTX administration (0.05, 0.1 and 0.2 m/kg/day) resulted in significant dos e-dependent inhibition of arthritis-induced changes, and the effects of MTX were similar between the two age groups. MTX was useful at each age. These results suggest that 4-month-old rats with arthritis are more appropriate as a model for evaluation of drugs for bone metabolic turnover in human chr onic rheumatoid arthritis.